This track collection shows Combined Annotation Dependent Depletion score. +CADD is a tool for scoring the deleteriousness of single nucleotide variants as well as insertion/deletions variants in the human genome. +
+ ++Many mutation annotations +tend to exploit a single information type (e.g. conservation) and/or are +restricted in scope (e.g. to missense changes). Thus, a broadly applicable +metric that objectively weights and integrates diverse information is needed. +Combined Annotation Dependent Depletion (CADD) is a framework that integrates +multiple annotations into one metric by contrasting variants that survived +natural selection with simulated mutations. +
+ ++C-scores strongly correlate with allelic diversity, pathogenicity of both +coding and non-coding variants, and experimentally measured regulatory effects, +and also highly rank causal variants within individual genome sequences. +Finally, C-scores of complex trait-associated variants from genome-wide +association studies (GWAS) are significantly higher than matched controls and +correlate with study sample size, likely reflecting the increased accuracy of +larger GWAS. +
+ ++There are four subtracks of this track: four for every possible single nucleotide mutation, +one for insertions and one for deletions. All subtracks show the CADD Phred score on mouse over. +
+ +
+For single nucleotides, at every +nucleotide position, with three values per position, one for every possible +mutation. +For the single nucleotide variants, please zoom in until you can see every basepair. The mouse overs +will other show averages over all nucleotides under the cursor, which is indicated by the prefix "~" +in the mouse over text. +
+ +The scores are also shown on mouse over for a set of insertions and deletions. On hg38, the selected +set has been obtained from Gnomad3. On hg19, it has been obtained from XXX (TODO: ask CADD authors). +
+ ++The raw data can be explored interactively with the Table Browser +or the Data Integrator. + +
+For automated download and analysis, the genome annotation is stored in a bigWig file that +can be downloaded from +our download server. +The files for this track are called a.bw, c.bw, g.bw, t.bw, ins.bb and del.bb. Individual +regions or the whole genome annotation can be obtained using our tool bigWigToWig +which can be compiled from the source code or downloaded as a precompiled +binary for your system. Instructions for downloading source code and binaries can be found +here. +The tool +can also be used to obtain only features within a given range, e.g. +bigWigToBedGraph http://hgdownload.soe.ucsc.edu/gbdb/$db/cadd/a.bw stdout
+ + ++Data were converted from the files provided on +the CADD Downloads website, provided by the Kircher lab, +using custom Python scripts, +documented in our makeDoc files. +
+ ++Thanks to the Kircher lab for providing the data. +
+ ++Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. + + A general framework for estimating the relative pathogenicity of human genetic variants. +Nat Genet. 2014 Mar;46(3):310-5. +PMID: 24487276; PMC: PMC3992975 +
+ ++Rentzsch P, Witten D, Cooper GM, Shendure J, Kircher M. + + CADD: predicting the deleteriousness of variants throughout the human genome. +Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894. +PMID: 30371827; PMC: PMC6323892 +
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